Inflammatory bowel diseases, represented by Crohn's disease and ulcerative colitis, are intractable diseases that often develop at relatively young ages and cause abdominal pain, fever, diarrhea, hematochezia and other symptoms. Crohn's disease is a granulomatous inflammatory disease of unknown cause that affects any part of the gastrointestinal tract from mouth to anus in a discontinuous manner. The disease progresses from ulcer to fibrosis and stricture, involving all layers of the bowel wall from mucosa to serosa. It is associated with systemic symptoms such as abdominal pain, chronic diarrhea, fever and malnutrition. On the other hand, ulcerative colitis is characterized by diffuse nonspecific inflammation of the large intestine of unknown cause. The disease primarily affects mucosa and often forms erosions and ulcers. It is also associated with various systemic symptoms including bloody diarrhea. Inflammatory bowl disease also refers to other inflammatory disorders in small and large intestines, including intestinal Behcet's disease, ulcerative colitis, bleeding rectal ulcer and pouchitis. Although it is believed that the etiology of inflammatory bowel diseases involves abnormal immune function, the exact cause of the diseases still remains unknown (Non-Patent Documents 1 and 2).
Medications for inflammatory bowel diseases include immunosuppressors, steroids, salazosulfapyridine and mesalazine. While immunosuppressors, in particular antimetabolites such as azathiopurine and 6-mercaptopurine, are considered effective against Crohn's disease, the drugs exhibit low efficacy at an early stage of administration and often cause allergies, pancreatitis, leukopenia and other side effects. High doses of cyclosporine are effective against inflammatory and fistulous diseases, but the drug cannot be used for a prolonged period due to its toxicity. Infliximab, a monoclonal antibody that inhibits a tumor necrosis factor, is administered by intravenous infusion to treat moderate or serious Crohn's disease (especially those accompanied by fistula) resistant to other treatments. However, long-term effects and side effects of the treatment are unknown. Other potential immunosuppressors include interleukin-1 blockers, anti-interleukin-12 antibodies, anti-CD4 antibodies, adhesive molecule inhibitors, and monoclonal antibodies against down-regulatory cytokines and tumor necrosis factors. Each of the current therapeutic approaches for the treatment of inflammatory bowel diseases has its own disadvantages. Thus, there is a need for more effective and safe medications (Non-Patent Documents 3, 4 and 5).
2-amino-1,3-propanediol derivatives described in the present application are known as effective immunosuppressors used to prevent rejection in organ transplantation (Patent Literatures No. 1 and 2). While 2-amino-1,3-propanediol derivatives have been known to act as sphingosine-1-phosphate receptor agonists, their usefulness in the treatment of inflammatory bowel diseases has never been described.    [Non-Patent Document 1] 1997 Annual Report by the Research Committee of Intractable Inflammatory Bowel Disorders: The Ministry of Health and Welfare of Japan.    [Non-Patent Document 2] New Engl J Med, 2002, 347: 417-429    [Non-Patent Document 3] Am J Gastroenterol, 2001, 96: 1977-1997    [Non-Patent Document 4] Nucl Med Commun, 2005, 26:649-655    [Non-Patent Document 5] Saishin Igaku 2004, 59:1070-1075    [Patent Document 1] WO2003/029184 Pamphlet    [Patent Document 2] WO2003/029205 Pamphlet